Key Points• Del(18p), together with del(17p)/TP53 mutations, is present at a high frequency before ibrutinib treatment.• BTK mutations drive ibrutinib relapse, but del(17p)/TP53 mutations may be dispensable.Ibrutinib has generated remarkable responses in patients with chronic lymphocytic leukemia (CLL), including those with an unfavorable cytogenetic profile. However, patients develop resistance, with poor outcomes and no established treatment options. Mutations in BTK and PLCG2 have emerged as main mechanisms of drug resistance, but not all patients carry these mutations. Further understanding of mechanisms of resistance is urgently needed and will support rational development of new therapeutic strategies. To that end, we characterized the genomic profiles of serial samples from 9 patients with ibrutinib-relapsed disease, including 6 who had Richter transformation. Mutations, indels, copy-number aberrations, and loss of heterozygosity were assessed using next-generation sequencing and single-nucleotide polymorphism array. We found that 18p deletion (del(18p)), together with del(17p)/TP53 mutations, was present in 5 of 9 patients before ibrutinib therapy. In addition to BTK C481 , we identified BTK T316A, a structurally novel mutation located in the SH2 domain of BTK. Minor BTK clones with low allele frequencies were captured in addition to major BTK clones. Although TP53 loss predisposes patients for relapse, clone size of TP53 loss may diminish during disease progression while mutant BTK clone expands. In patients who had Richter transformation, we found that the transformed cells were clonal descendants of circulating leukemia cells but continued to undergo evolution and drifts.Surprisingly, transformed lymphoma cells in tissue may acquire a different BTK mutation from that in the CLL leukemia cells. Collectively, these results provide insights into clonal evolution underlying ibrutinib relapse and prompt further investigation on genomic abnormalities that have clinical application potential.

codes of ethics, isomorphism, organizational legitimacy, strategic legitimacy,

Purpose -The purpose of this paper is to contribute to existing critiques of workplace spirituality and organizational culture. The paper links the two by problematising definitions of workplace spirituality that employ a "culture approach" to change, in which the construct is limited to a set of values that gives particular meaning to the workplace. Design/methodology/approach -Properties of Weick's sensemaking model combined with a critical sensemaking approach are used to analyze texts in order to show how a spiritual culture may shape the actions of its members by serving as an implicit form of managerial control. Findings -The paper reveals how some texts, Mitroff and Denton's, in particular, advocate workplace spirituality as necessary for organizations and the individuals who work in them to prosper. Simultaneously, such texts may imply a form of pastoral power, the purpose of which is to re-affirm a positive self-image, due to the cueing effects of language that is voiced in specific contexts. Practical implications -The paper suggests that a cultural approach to understanding workplace spirituality influences how people can make sense of the organization in which they are members. The potential inordinate reverence of work and one's contribution toward enhanced organizational performance is of interest to all members of organizations because it highlights how control is achieved. Originality/value -The paper offers some insights into the conditions that promulgate the linkage between work and spiritual fulfilment, and it promotes the continuing development of critical spirituality in organizations in order to overcome the potential managerial instrumentality that is highlighted in this paper.

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PurposeThe paper seeks to promote the integration of reflective learning within a broader service learning pedagogy at the undergraduate university level. Furthermore, it aims to illustrate various models for service learning that span multiple academic disciplines.Design/methodology/approachThe paper illustrates three ways in which reflective learning can be used to enhance the learning potential of service learning pedagogy. The subjective experiences inform its own stories that it presents as examples, supported as they are by the findings of prior empirical studies.FindingsThe paper believes that multi‐dimensional learning has been achieved in each of the three examples presented. Service learning extends the academic learning of students and allows for personal and societal learning to occur, not simply as a result of having a service experience, but of spending time reflecting on it.Practical implicationsPractical implications are particular to the students themselves, as the service experiences it describes have, in some instances, helped to clarify individual students' values and vocational interests.Social implicationsGiven the range of service learning models contained in these examples, the social implications likewise range, yet share common dimensions of increasing students' social consciousness, appreciation of diversity, and their own capacities to contribute.Originality/valueThe originality of this paper lies in the linking of reflective learning to service learning best practices to highlight the particular role of reflection in the production of multi‐dimensional learning.